March 13, 2018

Role of Skin Barrier Dysfunction in Canine Atopic Dermatitis

Alterations in lipid properties in atopic canine skin are similar to the changes seen in humans with the condition.
By Natalie Stilwell, DVM, MS, PhD
Atopic dermatitis (AD) is a common chronic inflammatory and pruritic skin disease in dogs. While the pathogenesis of canine AD is not completely understood, human studies show an association between AD and abnormal skin barrier function. Namely, alterations to the stratum corneum, the skin’s outermost layer, are believed to compromise the skin barrier and allow easier entry of allergens and pathogens into the skin.

Specific lipid abnormalities within the stratum corneum of human AD skin samples include decreased total lipid content, reduced free fatty acids and ceramide chain length, and less organized lipid packing.

An article published last month determined that, similar to humans, skin barrier dysfunction plays an important role in canine AD.

Analyses
Researchers assessed skin biopsy samples from 3 control beagle dogs ranging in age from 1 to 3 years and 5 Bedlington beagle crossbreed dogs with AD ranging from 2 to 9 years of age. In the AD dogs, the Canine Atopic Dermatitis Extent and Severity Index (CADESI) was used to calculate severity of AD lesions at several local anatomic sites, as well as a total body score determined from 62 body sites.

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Biopsies were obtained from lesional sites on the axilla, trunk, and inguinal regions, as well as from nonlesional sites on the trunk. After the stratum corneum was isolated from biopsy samples, several methods of analysis were performed, including small-angle X-ray diffraction (SAXD), Fourier transform infrared spectroscopy (FTIR), high-performance thin-layer chromatography (HPTLC), and liquid chromatography/mass spectrometry (LC/MS).

Results
Control and nonlesional AD skin samples possessed local CADESI scores of 0, indicating no signs of AD disease. Lesional AD skin samples had local CADESI scores ranging from 1 to 3 out of 5, indicating mild to moderate AD. 

Important findings:
  • SAXD revealed altered lamellar organization, including reduced free fatty acid levels, in the stratum corneum of AD lesion biopsies when compared with nonlesional AD and control skin samples. This finding suggests increased permeability of the skin barrier and, hence, reduced skin barrier function.
  • FTIR revealed altered lateral packing in the stratum corneum, resulting in disordered conformation and a compromised skin barrier. Similar results have been observed in human AD studies.
  • HPTLC and LC/MS revealed altered stratum corneum lipid properties similar to changes seen in human AD patients. While the relative abundance of cholesterol, total ceramides, and ceramide subclasses was similar among all samples, free fatty acids were relatively less abundant in lesional AD samples compared with controls. Also, reduced ceramide chain lengths correlated with AD severity, as measured by CADESI scores. 

Implications
The changes in lipid composition and organization observed in canine lesional AD skin samples agree with changes observed in earlier human AD studies. These abnormalities are believed to compromise normal skin barrier structure and function, leading to easier entry of allergens and pathogens into the skin. Studies like these are integral to increasing understanding of AD pathogenesis in the dog and, hopefully, improving therapeutic design for this extremely common disease.

 
Dr. Stilwell received her DVM from Auburn University, followed by a MS in Fisheries and Aquatic Sciences and a PhD in Veterinary Medical Sciences from the University of Florida. She provides freelance medical writing and aquatic veterinary consulting services through her business, Seastar Communications and Consulting.

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